The overall objective of this research is to develop an effective treatment plan using adoptive immunotherapy in combination with chemoradiotherapy for spontaneous leukemia in AKR mice. In particular, the beneficial effects of bacterial decontamination and isolation in a protected environment are being studied. Procedures for elimination of bacteria from the intestinal tract have been successfully applied to AKR mice after diagnosis of spontaneous acute T cell leukemia. Leukemic mice are rendered bacteria-free by continuous treatment per os with high dose antibiotics; a sterile laminar airflow environment is used to protect decontaminated mice from exogenous microorganisms. Leukemia remission induction with chemotherapy is essential to keep a significant proportion of leukemic mice alive during decontamination. For hematopoietic support and adoptive immunotherapy, mice undergoing decontamination are injected with bone marrow cells from conventional H-2 compatible or incompatible donor mice. Adoptive immunotherapy when applied to decontaminated leukemic AKR mice in remission can result in significant long-term leukemia-free survival without apparent secondary disease. Leukemia-free chimeras can be returned to the conventional environment. Experiments using the experimental treatment model to answer important questions concerning the clinical applicability of this model are continuing.